Patent NZ-510098-A (NZ)
Title: Substituted phenyl derivatives, pharmaceuticals thereof and their use as blockers of the chloride channel
Inventor: DAHL BJARNE H
IPC: C07C233/00
Filed: 1999-10-19
Abstract: A  compound having the formula I or a pharmaceutically acceptable salt thereof wherein one of R1 represents tetrazolyl,  R4, R5 and R2  are each  independently selected from hydrogen,  alkyl,  alkoxy, hydroxy,  halogen,  trifluoromethyl,  cyano,  nitro,  amino, alkylamino,  NHCOR9, CO2R9, -CON(R9)2, -NHSO2-R, -SO2N(R9)2, or   aryl  optionally  substituted  with  CON(R9)2,  NHCOR9, SO2N(R9)2, CO2R9. R9  represents hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl,  alkynyl, aryl, aralkyl, heteroaryl.  R9  may  also comprises  a 5-8 membered ring optionally containing  double bonds  and  optionally containing one  or  two  heteroatoms, which can be substituted by alkyl or acyl; or (R9)2 together with the heteroatom to which it is connected represents a 5- 8  membered  ring  optionally containing  double  bonds  and optionally  containing  another  heteroatom  which  can   be substituted by alkyl or acyl; aryl. R3 represents halogen or aryl where the aryl may be substituted one ore more times with substituents selected alkyl, hydroxy, alkoxy, halogen, trifluoromethyl, cyano, nitro, amino, NHCOR, CO2R, -CON(R)2, -NHSO2-R, -SO2N(R)2 wherein R9 is as defined above. Y represents -NHCONH R11, R12, R13, R14 and R15 are each independently selected from hydrogen, alkyl, alkoxy, halogen, trifluoromethyl, cyano, nitro, amino, alkylamino, -COOR7, -NHSO2-alkyl, SO2N(R)2; -SO2OR7, -CO-R7, aryl, phenylamino, phenoxy or heteroaryl. The phenyl, aryl or heteroaryl group may be substituted one or more times with substituents selected from alkyl, hydroxy, alkoxy, halogen, trifluoromethyl, cyano, nitro, amino and alkylamino, -COOR7; CON(R7)2. -NHSO2-R7; - SO2N(R7)2; -SO2OR7, or -CO-R7. It may also be one of R11 and R12, R12 and R13, R13 and R14, and R14 and R15 together form a 4-8 membered saturated or unsaturated ring and the other substituents R11, R12, R13, R14 and R15 as defined above. R7 represents hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, aryl, aralkyl, heteroaryl or Rcomprises a 5-8 membered ring optionally containing double bonds and optionally containing one or two heteroatoms which can be substituted by alkyl or acyl; or (R7)2 together with the heteroatom to which it is connected represents a 5-8 membered ring optionally containing double bonds and optionally containing another heteroatom which can be substituted by alkyl or acyl. However, the above compounds may not include: N-3-Trifluoromethylphenyl-N'-[4-bromo-2-(tetrazol-5- yl)phenyl] urea, or N-3-Bromophenyl-N'-[4-bromo-2-(tetrazol-5-yl)phenyl] urea, or N-3-Trifluoromethylphenyl-N'-[4-phenyl-2-(tetrazol-5- yl)phenyl] urea, or N-3-Trifluoromethylphenyl-N'-[4-[4-(4-trifluoromethylphenyl)- 2-(tetrazol-5-yl)phenyl] urea, or N-3-Trifluoromethylphneyl-N'-[4-(4-(4-ethoxycarbonylphenyl)- 2-(tetrazol-5-yl)phenyl] urea, or N-3-Trifluoromethylphneyl-N'-[4-(4- diethylaminocarbonylphenyl)-2-(tetrazol-5-yl)phenyl] urea, or N-3-Trifluoromethylphenyl-N'--[4-(4-aminocarbonylphenyl)-2- (tetrazol-5-yl)phenyl] urea, or N-3-Trifluoromethylphenyl-N'-[4-(4-carboxyphneyl)-2- (tetrazol-5-yl)phenyl urea, or N-3-Trifluoromethylphenyl-N'--[4-(4-anilinocarbonylphenyl)-2- (tetrazol-5-yl)phenyl] urea, or N-3-Biphenyl-N'-[4-bromo-2(tetrazol-5-yl)phenyl urea, or- N-3-(3-Pyridyl)phenyl-N'-[4-bromo-2-(tetrazol-5-yl)phenyl] urea. The compounds as described above may treat sickle-cell anaemia, brain oedema following ischaemia, or tumours, diarrhea, hypertension (diuretic), bone metabolic disorders, osteoclast associated disorders, bone metastasizing cancers, glaucoma, allergic or inflammatory conditions or healing ulcers.